PXD047166

PXD047166 is an original dataset announced via ProteomeXchange.

Title	Signal Regulatory Protein Beta 2 is a novel positive regulator of innate anticancer immunity, GFP-IP/MS of SIRP-B2 on THP-1
Description	In recent years, the therapeutic (re)activation of innate anticancer immunity has gained prominence, with therapeutic blocking of the interaction of Signal Regulatory Protein (SIRP)-α with its ligand CD47 yielding complete responses in refractory and relapsed B cell lymphoma patients. SIRP-α has as crucial inhibitory role on phagocytes, with e.g., its aberrant activation enabling the escape of cancer cells from immune surveillance. SIRP-α belongs to a family of paired receptors comprised of not only immune-inhibitory, but also putative immune-stimulatory receptors. Here, we report that an as yet uninvestigated SIRP family member, SIRP-beta 2 (SIRP-ß2), is strongly expressed under normal physiological conditions in macrophages and granulocytes at protein level. Endogenous expression of SIRP-ß2 on granulocytes correlated with trogocytosis of cancer cells. Further, ectopic expression of SIRP-ß2 stimulated macrophage adhesion, differentiation and cancer cell phagocytosis as well as potentiated macrophage-mediated activation of T cell Receptor-specific T cell activation. SIRP-ß2 recruited the immune activating adaptor protein DAP12 to positively regulate innate immunity, with the charged lysine 202 of SIRP-ß2 being responsible for interaction with DAP12. Mutation of lysine 202 to leucine lead to a complete loss of the increased adhesion and phagocytosis. In conclusion, SIRP-ß2 is a novel positive regulator of innate anticancer immunity and a potential costimulatory target for innate immunotherapy.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:16:46.424.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Nienke Visser
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-11-22 04:01:12	ID requested
1	2023-12-04 04:15:46	announced
⏵ 2	2024-10-22 06:16:46	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: LC-MSMS,SIRPB2, THP-1, GFP-IP

Edwin Bremer
contact affiliation	Department of hematology, UMCG
contact email	e.bremer@umcg.nl
lab head
Nienke Visser
contact affiliation	University Medical Center Groningen (UMCG)
contact email	n.visser@umcg.nl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD047166
     1. Label: PRIDE project
     2. Name: Signal Regulatory Protein Beta 2 is a novel positive regulator of innate anticancer immunity, GFP-IP/MS of SIRP-B2 on THP-1